1. Field of the Invention
The present invention relates generally to compositions and methods of using them for prevention or treatment of disorders of the prostate gland. More specifically, the invention relates to compositions and methods for prevention or treatment of prostate carcinoma, benign prostate hyperplasia or prostatitis, and for relieving symptoms and improving objective signs of such prostate disorders.
2. Background of the Technology
Currently, thousands of drugs commonly used and prescribed today are either derived from a plant source or contain chemical imitations of a plant compound. Many of these medicinal formulations contain herbal components or extracts from herbs. Technically speaking, an herb is a small, non-woody (i.e., fleshy stemmed), annual or perennial seed-bearing plant in which all the aerial parts die back at the end of each growing season. As the word is more generally used and as it is used herein, an herb is any plant or plant part which has a medicinal use. Thus, the term herb is also generally used to refer to the seeds, leaves, stems, flowers, roots, berries, bark, or any other plant parts that are used for healing.
Traditionally, dietary supplements referred to products made of one or more of the essential nutrients, such as vitamins, minerals, and protein. Passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA) broadened the definition to include, with some exceptions, any product intended for ingestion as a supplement to the diet. This includes vitamins; minerals; herbs, botanicals, and other plant-derived substances; and amino acids (the individual building blocks of protein) and concentrates, metabolites, constituents and extracts of these substances. Dietary supplements are usually in a dosage form such as capsules, tablets, liquids, powders, soft gels, etc. and generally are not represented as a conventional food or as a sole item of a meal or of the diet (Dietary Supplement Health and Education Act of 1994, Section Three).
The passage of DSHEA established a new regulatory framework for dietary supplements (Dietary Supplement Health and Education Act, Public L. No. 103-417, 108 Stat. 4325 (1994)). DSHEA, which amends the Federal Food Drug and Cosmetic Act, allows supplement manufacturers to make certain limited statements of nutritional support for dietary supplements including a statement that: (1) claims a benefit to a classical nutrient deficiency disease and discloses the prevalence of such disease in the U.S.; (2) describes the role of a nutrient or dietary ingredient intended to affect the structure or function in humans; (3) characterizes the documented mechanism by which a nutrient or dietary ingredient acts to maintain such structure or function; or (4) describes general well-being from consumption of a nutrient or dietary ingredient (Dietary Supplement Health and Education Act, Public L. No. 103-417 xc2xa76, 108 Stat. 4325, 4329 (1994)).
Dietary supplements are available widely through many commercial sources including health food stores, grocery stores, pharmacies, and by mail. Historically in the United States, the most prevalent type of dietary supplement was a multivitamin/mineral tablet or capsule that was available in pharmacies by prescription or xe2x80x9cover the counter.xe2x80x9d Supplements containing strictly herbal preparations were less widely available. Currently in the United States, a wide array of supplement products are available and they include vitamin, mineral, other nutrients, and botanical supplements as well as ingredients and extracts of animal and plant origin.
The prostate gland (or prostate) is a walnut-sized, mucous-producing organ in males that lies just below the urinary bladder. The prostate typically grows and enlarges throughout life. The only known function of the prostate is to produce a secretion that nourishes and protects the sperm during reproduction. The urethra, the canal that in most mammals discharges urine from the bladder, passes through the prostate gland. Unfortunately, this anatomical feature creates problems, often associated with difficulty in urination, as males age.
In men, the prostate gland is the source of several common disorders including prostatitis and benign prostatic hyperplasia (BPH), wherein the prostrate gland becomes inflamed or enlarged. Prostatitis is defined as an inflammation or infection of the prostate gland. While prostatitis may be acute, associated with systemic findings of fever, chills and rigors, most cases of prostatitis are chronic and tend to be incurable with relatively frequent recurrences despite optimal standard therapy. Chronic prostatitis (inflammation or infection of the prostate) is common to all adult men. It is associated with virtually all cases of prostate cancer and is present in every prostate biopsy regardless of other findings. Chronic prostatitis may not cause significant symptoms in many men, but in others it can be a devastating disease that severely affects the quality of life of those afflicted. It is difficult to diagnose and even more difficult to treat.
The most common symptom of chronic prostatitis is pelvic pain, followed by various voiding symptoms, impotence, and infertility. Pain from prostatitis is usually located in the groin, testicles, and penis, just above the rectum or in the suprapubic area over the bladder. Pain is frequently associated with ejaculation. Typical voiding symptoms produced by prostatitis include getting up at night to void (nocturia), frequency and urgency of urination, incomplete voiding, decreased force of the urinary stream, intermittency of the stream and a need to push or strain to void. Impotence or erection difficulties and male infertility are also associated with prostatitis.
U.S. Pat. No. 6,197,309 to Wheeler discloses a prostate formula composition said to provide an all-natural, non-surgical preventative of or improvement to disorders of the prostate gland, particularly, prostatitis, and for relieving symptoms and improving objective signs of prostatitis. The formula of the composition preferably includes the following ingredients each in a therapeutically effective amount: Vitamin C, Vitamin B6, Vitamin E, zinc, glycine, L-alanine, Glutamic acid, Saw palmetto, Pygeum extract, Pumpkin seed, Stinging nettle, Echinacea, garlic, Ginkgo leaves, and selenium.
According to Wheeler, supra., a wide variety of therapies for prostatitis are available, but few actually work in more than a small percentage of cases. None of the standard treatments is able to improve the health and well being of the prostate.
In the treatment of prostatitis, physicians have traditionally recommended everything from doing nothing to multiple and extended courses of antibiotics, other drugs, and lifestyle changes. Those patients who truly have an identifiable infection of the prostate benefit from antibiotics. These need to be continued for at least 6-12 weeks and, in some cases, long-term or indefinite antibiotic suppression therapy is necessary.
BPH occurs naturally in most males over 50 years of age. At this age, the male body begins to transform testosterone (male sex hormone) into dihydroxytestosterone (DHT) at higher levels within the prostate. This is primarily due to the higher levels of the enzyme reductase, which causes the conversion of testosterone to DHT. DHT has a tendency to bind to prostatic receptor cells, which ultimately results in prostate enlargement. It is usually a benign condition, and therefore, in some cases there is no need for surgery. However, enlargement of the prostate gland can cause many uncomfortable and annoying symptoms. Worsening symptoms may require prostate surgery. Nearly 400,000 prostate surgical procedures are performed annually to treat enlarged prostates. Numerous laboratories are conducting research in an attempt to find a cure for BPH.
Further, according to Wheeler, supra., treatments for prostate disorders include alpha blockers, e.g., HYTRIN (terazosin HCl, Abbott Laboratories, Abbott Park, Ill.), CARDURA (Roerig Pharmaceuticals, Alexandria, Va.) and FLOMAX (tamsulosin HCl, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Conn.), which are designed to relax the muscle tension in the prostate and improve urinary flow. They do tend to improve voiding difficulties and relax tension in the prostate. However, they are expensive, need to be taken indefinitely in high doses, may often have significant side effects and do not cure the underlying problem or prevent recurrences.
There are also other treatments for prostate disorders. For example, PROSCAR (finasteride, Merck Human Health, White House Station, N.J.) can shrink prostate tissue, but there is no proof it helps in the treatment of prostatitis. Allopurinol, a drug that reduces uric acid levels in the body, has been used to treat prostatitis based on the theory that uric acid crystals may form in the prostate and cause inflammation. Anti-inflammatory agents, such as ibuprofen, and hot sitz baths have been helpful in treating the discomfort caused by prostatitis in many patients, but neither of these treatments actually cures the disease and the benefits wear off rapidly.
Irritative voiding symptoms may be relieved by bladder relaxing agents such as oxybutynin (DITROPAN Alza Corporation, Palo Alto, Calif.), while antidepressants such as amitriptyline (ELAVIL AstraZeneca, Wilmington, Del.) have been helpful in various chronic pain conditions such as prostatitis associated with depression. Biofeedback, behavioral therapy, referral to a pain clinic and psychological treatment have all been recommended for patients with prostatitis and occasionally offer some relief to selected individuals. For the most part, current treatment methods for prostatitis are generally rather disappointing.
Prostatic massage plus antibiotics has been used with some success. However, proponents of prostatic massage (championed in the Philippines) have little reproducible data to support their methods. Other drawbacks include intense discomfort/pain at the time of massage, the need for accurate cultures of the prostatic fluid, and a dependence on antibiotics to ultimately effect the cure.
There are natural elements that have known benefits in treating enlargement of the prostate gland and prostatitis. It is widely accepted that zinc has positive effects in reducing an enlarged prostate, but studies have indicated that zinc administered orally does not reach prostatic tissue very effectively. Therefore, the prostate does not reap its full benefits. Other studies have shown that Pygeum africanum extract has definite effects in reducing the size of the prostate. Extensive studies have shown that Saw palmetto (Serenoa repens) effectively reduces the size of the enlarged prostate and restores function. Another natural product known to produce beneficial effects on the enlarged prostate is pumpkin seed. Pumpkin seeds have been used as a folk remedy for centuries, and it is believed that Hungarian gypsies, Ukrainians and Transylvanians do not suffer from BPH because they eat pumpkin seeds from childhood as part of their daily diet. Additionally, according to Wheeler, supra., the Chinese use a combination of three amino acids: glycine, L-alanine, and glutamic acid, to treat disorders of the prostate. PROSTAMAX (Hankintatukku Natural Products Co., Helsinki, Finland) is a prostate formula on the market, having a per tablet formula of Vitamin C, 10 mg; Vitamin B6, 10 mg; Vitamin E (succinate), 5 IU; zinc chelate, 10 mg; L-glycine, 120 mg; alanine, 120 mg; Saw palmetto, 106 mg; Pygeum africanus extract, 10 mg; Pygeum africanus herb, 20 mg; pumpkin seed, 200 mg; Stinging nettle leaves, 75 mg; Echinacea, 25 mg; Ginkgo biloba, 20 mg; Wild yam, 20 mg; and Uva ursi, 10 mg.
U.S. Pat. No. 5,736,144 to Gideon describes a medicinal tea made from radishes. The tea is used as an anti-microbial or anti-inflammatory agent and is reportedly effective in treating prostatitis.
U.S. Pat. No. 4,258,037 to Juvin describes a therapeutic composition said to be useful for the treatment of both male and female urogenital disorders such as prostatic disorders and bartholinitis. The composition contains Pygeum or other extracts of the trees of the Rosaceae-family, together with a mono-aminated amino acid such as glycine, L-glutamic acid or L-alanine.
U.S. Pat. No. 5,543,146 to Perez describes a dietary supplement composition for alleviating the symptoms associated with enlargement of the prostate gland. The composition includes pumpkin seeds, zinc, magnesium, vitamin E, Saw palmetto, and Pygeum africanum, but does not include stinging nettle, zinc, garlic, ginkgo, glutamic acid, alanine, glycine, Echinacea and Uva ursi. 
Prostate carcinoma is a major cause of death among men. In the U.S., recent estimates indicate that well over 300,000 men are diagnosed with prostate cancer each year. While many of the small, localized prostate cancer appear not to be life-threatening, those that spread to other sites in the body are almost invariably fatal. Conventional treatment includes radical prostactomy, nerve-sparing prostatectomy, external-beam radiation, seed radiation, cryotherapy and hormone therapy. Each of these therapies has serious side effects and other limitations, and recurrence frequently occurs.
Serum PSA (Prostate Specific Antigen) is a diagnostic parameter that has been used to monitor the stages of prostrate cancer development and the progress of the therapy. Serum PSA measures the substance emitted both by the normal prostate gland and by cancerous tissue in the prostate gland. With normal prostate gland, PSA reads between 0 to 4. Elevated PSA (higher than 5) indicates a sign of prostate carcinoma, benign prostate hyperplasia or prostatitis. The higher the PSA reading, the larger the volume of the cancer.
U.S. Pat. No. 5,665,393 to Chen. et al. discloses an herbal composition for treating prostate conditions comprising material from the following herbs: Panax pseudo-ginseng Wall, Isatis Indigotica Fort, Ganoderma lucidum Karst, Dendranihema morifolium Tzvel, Glycyrrhiza glabra L., Scutellaria baicalensis Georgi, Rabdosia rubescens, Serenoa repens. Preferably, the material from each of such herbs is an alcohol extract of dried, cut plants and of the Panax. The pseudo-ginseng Wall and each of the other materials are present in a dried, weight-to-weight range of about 1:1-6. The composition is administered orally or by suppository. Chen further discloses combining administration of the herbal composition with administration of a therapeutically effective amount of an anticancer compound effective for prostate cancer, such as luteinizing hormone releasing hormone, estrogen, antiandrogen, gonadotrophin-releasing hormone and synthetic analogs thereof which have hormone activity, or of other agents generally effective for treatment of infections or malignancies, such as antibiotics, antimetabolites and cytotoxic agents.
U.S. Pat. No. 5,417,979 to Fan, et al., discloses a combination of the herbs Ganoderma lucidum Karst, Rabdosia rubescens and Glycyrrhiza glabra L. with other herbs for treatment of cancers other than prostate cancer.
U.S. Pat. No. 5,721,134 to Lee, et al. discloses Ganoderma lucidum KCCM 10045 which produces proteoglycan (G009) having an effect of antitumor immunity.
U.S. Pat. No. 4,613,591 to Aburada, et al. discloses an adminiculum for increasing the antitumor activities of mitomycin C and doxorubicin hydrochloride and decreasing the side effects associated with their use comprising an aqueous or aqueous organic solvent extract of a crude preparation of Astragali radix, Cinnamomi cortex, Rehmanniae radix, Paeoniae radix, Cnidii rhizoma, Atractylodis lanceae rhizoma, Angelicae radix, Ginseng radix, Hoelen and Glycyrrhizae radix. Also disclosed are a method for preparing this adminiculum and a method for its use. In addition, compositions and methods for treating tumor-bearing patients are disclosed.
U.S. Pat. No. 4,618,495 to Okuda, et al. discloses a composition for reducing cancer symptoms by improving lipid metabolism and eliminating or reducing anorexia in tumor-bearing patients through inhibition of the lipid degradation-promoting action of toxohormone L, which comprises an aqueous or aqueous organic solvent extract of one or more crude preparations selected from the group consisting of Astragali radix, Cinnamomi cortex, Rehmanniae radix, Paeoniae radix, Cnidii rhizoma, Atractylodis lanceae rhizoma, Angelicae radix, Ginseng radix, Hoelen and Glycyrrhizae radix. Also diclosed are a method for preparing such a composition, and a method for reducing cancer symptoms using the composition.
There is thus a need for compositions and methods for prevention and treatment of disorders of the prostate gland, particularly for prevention or treatment of prostate carcinoma, benign prostate hyperplasia or prostatitis, for relieving symptoms and improving objective signs of such prostate disorders, and for maintaining prostate health.
A primary object of the present invention is to provide a composition having beneficial effects in preventing and treating prostate disorders including prostatitis, benign prostate hyperplasia and prostatic carcinoma.
It is also an object of the invention to provide a composition that is beneficial to various symptoms of prostate disorders, including elevated blood levels of Prostate Specific Antigen (PSA) and irritative voiding symptoms such as getting up at night to void (nocturia) and otherwise excessive frequency and urgency of urination.
It is a further object of the invention to provide a composition for preventing and treating prostate disorders that has all natural ingredients, has no adverse side effects, has no interactions with any medication, and may be taken orally in solid or liquid form or in various other forms.
Yet another object of the invention to provide a method of preventing and treating prostate disorders and of maintaining prostate health using compositions of this invention.
These and other objects are satisfied by the present invention providing a composition comprising herbs and fungi or extracts thereof, which is useful to prevent or treat prostate disorders and which can also be used as a dietary supplement to maintain or improve prostate health. Combinations of herbs and fungi and extracts thereof, according to the invention, profoundly improve the conditions of patients with prostate disorders including prostatitis and prostate cancer, and alleviate symptoms such as elevated serum PSA levels and nocturia and otherwise excessive frequency and urgency of urination.
One embodiment of the composition of the invention comprises at least 44 particular herbal or other natural components, or extracts thereof. Preferably, the composition further comprises Ganoderma Lucidum. Preferably, material from each of the herbs or fungi is an aqueous extract of dried, cut plant or fungal parts. It is particularly preferred that the herbal components and each of the other materials are present in relative amounts (dried weight-to-weight ratios) that lie within particular ranges disclosed herein. Composition of the invention are preferably provided in an ingestible form, such as, for example, a powder, capsule or tablet.
The invention further provides methods of treating prostate disorders including prostatitis, benign prostate hyperplasia and prostatic carcinoma. One such method is for treating prostate cancer in an individual in need thereof which comprises administering a therapeutically effective amount of an herbal composition described herein. Preferably, the invention method further comprises administering a therapeutically effective amount of an anticancer compound effective for prostate cancer, selected from the group consisting of luteinizing hormone releasing hormone, estrogen, antiandrogen, gonadotrophin-releasing hormone and synthetic analogs thereof which have hormone activity. The invention also preferably provides such a method further comprising administering a therapeutically effective amount of a compound selected from the group consisting of antibiotics, antimetabolites and cytotoxic agents.
One aspect of the present invention, therefore relates to a composition comprising the following herbal and other components: Radix Asparagi; Radix Angelicae Pubescentis; Radix Trichosanthis; Radix Scuttellariae; Radix Angelicae Sinensis; Radix Dipsaci; Cortex Eucommiae; Medulla Junci; Rhizoma Anemarrhenae; Caulis Akebiae; Herba Dianthi; Semen Plantaginis; Cortex Phellodendri (fried); Radix et Rhizoma Rhei; Rhizoma seu Radix Notopterygii; Olibanum; Fructus Gardeniae; Radix Astragali seu Hedysari; Rhizoma Cimicifugae; Radix Bupleuri; Myrrha; Gypsum Fibrosun; Radix Rehamanniae (crude); Folium Pyrrosiae; Rhizoma Acori Graminei; Rhizoma Dioscoreae Hypoglaucae; Radix Linderae; Herba Cistanche; Radix Paeoniae Rubra; Rhizoma Dioscoreae; Semen Euryales; Cortex Mouton; Polyporus Umbellatus; Radix Rehmanniae Praeparata; Medulla Tetrapanacis; Semen Coicis; Fructus Horedi Germinatus (Poria); Radix Aconiti Praeparata; Rhizoma Alismatis; Cortex Cinnamomi; Herba Asari; Radix Glycyrrhizae; Stigma Maydis; and Phaseolus Radiatus L. In a preferred embodiment, this composition further comprises Ganoderma Lucidum. 
Additional embodiments of the compositions of the present invention include a composition described above, further comprising at least one herbal or other component selected from the following group of components: Bulbus Lilii; Citri Reticulatae Viride; Cortex Moutan Radicis; Cortex Lycii Radicis; Faecs Trogropterori; Flos Lonicerae; Fructus Alpiniae Oxyphyllae; Fructus Aurantii Immaturus; Fructus Cnidii; Fructus Corni; Fructus Schisandrae; Fructus Arctii; Herba Cynomorii; Herba Epimedii; Herba Leonuri; Herba Polygoni Avicularis; Radix Achyranthis Bidentatae; Radix Aconiti Kusnezoffii; Radix Angelicae Dahuricae; Radix Aucklandiae; Radix Clematidis; Radix Codonopsis Pilosulae; Radix Gentianae Macrophyllae; Radix Ophiopogonis; Radix Paeoniae Alba; Radix Polygalae; Radix Stephaniae Tetrandrae; Ramulus Cinnamomi; Rhizoma Atractylodis; Rhizoma Belamcandae; Rhizoma Corydalis; Rhizoma Ligustici Chuanxiong; Rhizoma seu Radix Nototerygii; Rhizoma Zingiberis Recens; Semen Biotae; Semen Cuscutae; Semen Dolichoris Album; Semen Pharbitidis; Semen Persicae; Spica Prunellae; and Stigma Maydis.
Preferably, compositions of the present invention comprise an aqueous or alcohol or aqueous-alcohol extract of each specified herbal component. Other forms of the specified components are also contemplated, however, including mixtures of dried forms of the specified crude components, such as whole dried plants or plant parts, or powders of ground dried plants or part, or powders of extracts or decoctions of plants and other components.
In a particularly preferred embodiment, the invention composition comprises an aqueous extract of the following herbal and other components in the specified ratios of dry weights compared to the dry weight of the least abundant component (as recited in Table 2, supra.): Radix Asparagi (6:1); Radix Angelicae Pubescentis (6:1); Radix Trichosanthis (9:1); Radix Scuttellariae (4:1); Radix Angelicae Sinensis (1:1); Radix Dipsaci (1:1); Cortex Eucommiae (1:1); Medulla Junci (1:1); Rhizoma Anemarrhenae (4:1); Caulis Akebiae (8:1); Herba Dianthi (8:1); Semen Plantaginis (6:1); Cortex Phellodendri (fried) (8:1); Radix et Rhizoma Rhei (4:1); Rhizoma seu Radix Notopterygii (1:1); Olibanum (1:1); Fructus Gardeniae (7:1); Radix Astragali seu Hedysari (15:1); Rhizoma Cimicifugae (4:1); Radix Bupleuri (4:1); Myrrha (1:1); Gypsum Fibrosun (18:1); Radix Rehamanniae (crude) (15:1); Folium Pyrrosiae (9:1); Rhizoma Acori Graminei (6:1); Rhizoma Dioscoreae Hypoglaucae (6:1); Radix Linderae (6:1); Herba Cistanche (1:1); Radix Paeoniae Rubra (6:1); Rhizoma Dioscoreae (9:1); Semen Euryales (6:1); Cortex Mouton (1:1); Polyporus Umbellatus (6:1); Radix Rehmanniae Praeparata (1:1); Medulla Tetrapanacis (6:1); Semen Coicis (8:1); Fructus Horedi Germinatus (Poria) (9:1); Radix Aconiti Praeparata (6:1); Rhizoma Alismatis (6:1); Cortex Cinnamomi (3:1); Herba Asari (4:1); Radix Glycyrrhizae (3:1); Stigma Maydis (18:1); Phaseolus Radiatus L (31:1); and Ganoderma Lucidum (1:1).
Compositions of the invention, particularly compositions comprising extracts of the specified components, optionally further comprise a pharmaceutically acceptable carrier, diluent or additive, for use as a pharmaceutical composition. In another aspect, the invention provides a dietary supplement comprising a composition of the invention.
Preferred embodiments of compositions according to the present invention provide a composition of matter comprising a mixture of the herbal and other components listed in Table 2, wherein the components are present in the mixture in amounts such that the mixture is effective in a mammal for preventing or treating prostate disorders including prostatitis, benign prostate hyperplasia and prostatic carcinoma. Preferably, mammal in which this composition is effect is a human being susceptible to or suffering from a prostate disorder. In particular, such mixtures are effective for reducing serum levels of Prostate Specific Antigen (PSA) that are elevated above normal and for reducing irritative voiding symptoms of prostatitis.
In preferred embodiments of the invention composition, the mixture is effective for ameliorating at least one effect of a prostate carcinoma in a human or other mammal having such a tumor. Ameliorated effects of a prostate carcinoma include but are not limited to reducing the growth rate or mass of the carcinoma.
In another aspect, the present invention provides a method for prevention or treatment of prostate disorders in a mammal including prostatitis, benign prostate hyperplasia and prostatic carcinoma, comprising administering to the mammal a composition of matter of the invention, periodically for a time sufficient to achieve prevention or treatment of the prostate disorder in the mammal. In one embodiment of this method, the disorder is prostatic carcinoma and the administering is performed before surgery to remove the carcinoma, to reduce the tumor size and to cause better separation of the tumor from surrounding normal tissue. Preferably, the administering of an invention composition periodically is conducted once or twice daily, or at least about three to four times a week.
The method of treating prostatic carcinoma optionally further comprises administering a therapeutically effective amount of an anticancer compound effective for prostate cancer, selected from the group consisting of luteinizing hormone releasing hormone, estrogen, antiandrogen, gonadotrophin-releasing hormone and synthetic analogs thereof which have hormone activity, or a therapeutically effective amount of a compound selected from the group consisting of antibiotics, antimetabolites and cytotoxic agents. Method of using each of these agents for treating prostate cancer, prostatitis or other prostate conditions are well known in the art.
In yet another aspect, the invention provides a method of ameliorating symptoms associated with prostate disorders in a mammal, preferably a human being suffering from such a disorder, including prostatitis, benign prostate hyperplasia and prostatic carcinoma. This method comprises administering to the mammal a composition of matter of the invention periodically for a time sufficient to achieve the desired amelioration.